Combined effects of smoking and HIV infection on the occurrence of aging-related manifestations.

Both HIV-1 infection and smoking may contribute to the development of ageing-related manifestations affecting the prognosis of people living with HIV, but it is unclear whether HIV and smoking exert their effects independently or interact by potentiating each other. We conducted a cross-sectional study in 192 people living with HIV aged- and gender-matched with 192 HIV-uninfected controls, assessing the relative effect of HIV-1/smoking status on lung function (FEV1), bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), aortic pulse-wave velocity (PWV), insulin resistance (HOMA-IR) and renal function. In both unadjusted and adjusted analyses, FEV1, BMD and ASMI significantly differed according to smoking/HIV status, with the worst parameters found in HIV-1 infected patients currently smoking, and BMD and ASMI decreased to a lesser extent in HIV-1 infected patients formerly smoking (> 10 pack-years). Values in people living with HIV with < 10 pack-years exposure were of similar magnitude to those from controls. Regarding PWV, HOMA-R and eGFR, no significant differences were found, with the exception of eGFR values which were globally lower in HIV-1 infected patients. In conclusion HIV infection and smoking acted synergistically and were associated with a wasting phenotype combining muscle mass and bone mineral reduction.Clinical Trial Registration (registrar, website, and registration number), where applicable: CPP 10-023, 09-027, 10-034.

Complement-dependent mpox-virus-neutralizing antibodies in infected and vaccinated individuals.

Mpox virus (MPXV) caused a multi-country outbreak in non-endemic areas in 2022. Following historic success of smallpox vaccination with vaccinia virus (VACV)-based vaccines, the third generation modified vaccinia Ankara (MVA)-based vaccine was used as prophylaxis for MPXV, but its effectiveness remains poorly characterized. Here, we applied two assays to quantify neutralizing antibodies (NAbs) in sera from control, MPXV-infected, or MVA-vaccinated individuals. Various levels of MVA NAbs were detected after infection, historic smallpox, or recent MVA vaccination. MPXV was minimally sensitive to neutralization. However, addition of complement enhanced detection of responsive individuals and NAb levels. Anti-MVA and -MPXV NAbs were observed in 94% and 82% of infected individuals, respectively, and 92% and 56% of MVA vaccinees, respectively. NAb titers were higher in individuals born before 1980, highlighting the impact of historic smallpox vaccination on humoral immunity. Altogether, our results indicate that MPXV neutralization is complement dependent and uncover mechanisms underlying vaccine effectiveness.

Profound Defect of Amphiregulin Secretion by Regulatory T Cells in the Gut of HIV-Treated Patients.

The persistence of a leaky gut in HIV-treated patients leads to chronic inflammation with increased rates of cardiovascular, liver, kidney, and neurological diseases. Tissue regulatory T (tTreg) cells are involved in the maintenance of intestinal homeostasis and wound repair through the IL-33 pathway. In this study, we investigated whether the persistence of gut mucosal injury during HIV infection might be explained in part by a flaw in the mechanisms involved in tissue repair. We observed an increased level of IL-33 in the gut of HIV-infected patients, which is associated with an increased level of fibrosis and a low peripheral reconstitution of CD4+ T cells. Our results showed that intestinal Treg cells from HIV-infected patients were enriched in tTreg cells prone to support tissue repair. However, we observed a functional defect in tTreg cells caused by the lack of amphiregulin secretion, which could contribute to the maintenance of intestinal damage. Our data suggest a mechanism by which the lack of amphiregulin secretion by tTreg may contribute to the lack of repair of the epithelial barrier.

Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus.

BACKGROUND: An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. METHODS: HIV-HCV coinfected patients were enrolled in the Agence Nationale de Recherches sur le Sida et les hépatites virales (ANRS) CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. RESULTS: At baseline, median age of the study population (N = 1213) was 45.4 (interquartile range [IQR] 42.1-49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9-7.0) years, the incidence was 6.98 (95% confidence interval [CI], 5.19-9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78-6.00) for coronary and/or cerebral events, and 3.17 (2.05-4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06; 95% CI, 1.01-1.12), prior CVD (HR 8.48; 95% CI, 3.14-22.91), high total cholesterol (HR 1.43; 95% CI, 1.11-1.83), high-density lipoprotein cholesterol (HR 0.22; 95% CI, 0.08-0.63), statin use (HR 3.31; 95% CI, 1.31-8.38), and high alcohol intake (HR 3.18; 95% CI, 1.35-7.52) were independently associated with total ASCVD events, whereas undetectable baseline viral load (HR 0.41, 95% CI, 0.18-0.96) was associated with coronary and/or cerebral events. CONCLUSIONS: HIV-HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV RNA are essential to control cardiovascular risk.

Corrigendum: CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses.

This corrects the article DOI: 10.1038/nature21710.

CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses.

The persistence of the HIV reservoir in infected individuals is a major obstacle to the development of a cure for HIV. Here, using an in vitro model of HIV-infected quiescent CD4 T cells, we reveal a gene expression signature of 103 upregulated genes that are specific for latently infected cells, including genes for 16 transmembrane proteins. In vitro screening for surface expression in HIV-infected quiescent CD4 T cells shows that the low-affinity receptor for the immunoglobulin G Fc fragment, CD32a, is the most highly induced, with no detectable expression in bystander cells. Notably, productive HIV-1 infection of T-cell-receptor-stimulated CD4 T cells is not associated with CD32a expression, suggesting that a quiescence-dependent mechanism is required for its induction. Using blood samples from HIV-1-positive participants receiving suppressive antiretroviral therapy, we identify a subpopulation of 0.012% of CD4 T cells that express CD32a and host up to three copies of HIV DNA per cell. This CD32a+ reservoir was highly enriched in inducible replication-competent proviruses and can be predominant in some participants. Our discovery that CD32a+ lymphocytes represent the elusive HIV-1 reservoir may lead to insights that will facilitate the specific targeting and elimination of this reservoir.

[Facing the HIV/AIDS epidemic in Mexico: the response of the health sector]. / Haciendo frente a la epidemia de VIH/SIDA en México: una respuesta organizada?

OBJECTIVE: To analyze the challenges and accomplishments of the Mexican health system as it faced the HIV/AIDS epidemic over the 20 years since discovery of the virus. METHODS: A review of the relevant literature was done. The topics revised were: HIV/AIDS epidemiology, the early response of the health system and civil society, prevention and risk behaviors, care and treatment, and financing and resources allocation. DISCUSSION: In Mexico a rapid initial public response surely contributed to containing any early spread of the epidemic to select populations; whether that spread will continue to be contained is an open question. Sexual risk practices remain high not only among traditional risk populations but also among youth. Even though the epidemic remains concentrated in Mexico, principally among MSM and IDU, only 13% of public HIV prevention funds are directed to key populations at especially high risk of becoming infected or infecting others. In recent years antiretroviral coverage has increased rapidly with funding increasing from 30 to 367 million pesos from 2001 to 2003 and coverage now approaching 100%. Of all health spending on HIV/AIDS in the public sector, 82.4% is spent by the social security institutes and 17.6% by the Ministry of Health. The former provides medical care to about half of PLHA while the latter, in addition to caring for the other half, supports the large majority of prevention expenses. One of the challenges faced by the health system which has largely achieved universal antiretroviral coverage is how to provide quality care with appropriate monitoring, promotion of adherence and recognition and treatment of resistance and adverse effects--without dramatically increasing costs.

Haciendo frente a la epidemia de VIH/SIDA en México: ¿Una respuesta organizada? / Facing the HIV/AIDS epidemic in Mexico: The response of the health sector

Objetivo. Analizar los retos y logros de los sistemas de salud mexicano en la lucha contra el VIH/SIDA a 20 años del descubrimiento del virus. Material y métodos. Se realizó una revisión de la bibliografía pertinente para el caso de México. Los tópicos principales revisados son el perfil epidemiológico del VIH/SIDA; las primeras respuestas del sistema y de la sociedad civil hacia la epidemia; la prevención y los comportamientos de riesgo; atención y tratamiento con énfasis en cobertura y normas terapéuticas; y financiamiento y asignación de recursos. Discusión. En México se produjo una rápida respuesta inicial ante la epidemia que contribuyó a mantenerla limitada a ciertos grupos de la población, no obstante, sin garantizar la protección futura de la población general y de los grupos más afectados. Las prácticas sexuales de riesgo se mantienen elevadas tanto en los grupos considerados tradicionalmente con más prácticas de riesgo como entre los jóvenes. A pesar de que la epidemia en México se considera como concentrada, principalmente en hombres que tienes sexo con hombres (HSH) y usuarios de drogas inyectables (UDI), los esfuerzos de prevención no tienen la suficiente focalización: sólo 13% del gasto en prevención se encuentra dirigido a la población de mayor vulnerabilidad para contraer el VIH. Por otra parte, en los últimos años ha habido un incremento importante en materia de provisión de antirretrovirales: el gasto en los mismos pasó de 30 millones en el año 2001 a 367 millones de pesos para el año 2003 alcanzando una cobertura cercana a 100%. Del total del gasto público en VIH/SIDA, 82.4% lo ejerció la seguridad social y el restante 17.6% lo ejerció la Secretaría de Salud; los fondos de la seguridad social se destinan a la atención y tratamiento de alrededor de 50% de las personas viviendo con VIH/SIDA, mientras que de los de la Secretaría de Salud se financia la otra mitad y la mayor parte de los gastos en prevención. Uno de los retos a que se enfrenta el sistema de salud, que ha logrado una cobertura cercana a 100% de atención con antirretrovirales es el cómo proveer de una atención de calidad, con un monitoreo adecuado, promoción de la adhesión y reconocimiento del problema de resistencia y efectos secundarios, sin un incremento explosivo en los costos.

Objective. To analyze the challenges and accomplishments of the Mexican health system as it faced the HIV/AIDS epidemic over the 20 years since discovery of the virus. Methods. A review of the relevant literature was done. The topics revised were: HIV/AIDS epidemiology, the early response of the health system and civil society, prevention and risk behaviors, care and treatment, and financing and resources allocation. Discussion. In Mexico a rapid initial public response surely contributed to containing any early spread of the epidemic to select populations; whether that spread will continue to be contained is an open question. Sexual risk practices remain high not only among traditional risk populations but also among youth. Even though the epidemic remains concentrated in Mexico, principally among MSM and IDU, only 13% of public HIV prevention funds are directed to key populations at especially high risk of becoming infected or infecting others. In recent years antirretroviral coverage has increased rapidly with funding increasing from 30 to 367 million pesos from 2001 to 2003 and coverage now approaching 100%. Of all health spending on HIV/AIDS in the public sector, 82.4% is spent by the social security institutes and 17.6% by the Ministry of Health. The former provides medical care to about half of PLHA while the latter, in addition to caring for the other half, supports the large majority of prevention expenses. One of the challenges faced by the health system which has largely achieved universal antiretroviral coverage is how to provide quality care with appropriate monitoring, promotion of adherence and recognition and treatment of resistance and adverse effects - without dramatically increasing costs.